Department of Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Department of Gynecologic Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong, China.
J Int Med Res. 2020 Dec;48(12):300060520980940. doi: 10.1177/0300060520980940.
The present study aimed to evaluate the effects of cluster of differentiation (CD)4CD25 forkhead box p3 (Foxp3) regulatory T cells (Tregs) on unexplained recurrent spontaneous abortion (URSA) and the associated mechanisms.
The proportion of CD4CD25Foxp3 Tregs and inflammatory cytokine concentrations in the peripheral blood of women with URSA were measured by flow cytometry and enzyme-linked immunosorbent assay, respectively. CBA/JxDBA/2J mating was used to establish an abortion-prone mouse model and the model mice were treated with the Toll-like receptor 4 (TLR4) antagonist E5564 and the TLR4 agonist lipopolysaccharide.
The proportion of CD4CD25Foxp3 Tregs was decreased and the inflammatory response was increased in women with URSA. In the abortion-prone mouse model, E5564 significantly increased the proportion of CD4CD25Foxp3 Tregs, decreased the inflammatory response, and increased Foxp3 mRNA and protein expression. Lipopolysaccharide had adverse effects on the abortion-prone model.
These data suggest that CD4CD25Foxp3 Tregs regulate immune homeostasis in URSA via the TLR4/nuclear factor-κB pathway, and that the TLR4 antagonist E5564 may be a novel and potential drug for treating URSA.
本研究旨在评估簇分化（CD）4CD25叉头框 p3（Foxp3）调节性 T 细胞（Tregs）对不明原因复发性自然流产（URSA）的影响及其相关机制。
采用流式细胞术和酶联免疫吸附试验分别检测 URSA 患者外周血中 CD4CD25Foxp3 Tregs 的比例和炎性细胞因子浓度。CBA/JxDBA/2J 交配建立易流产小鼠模型，并用 Toll 样受体 4（TLR4）拮抗剂 E5564 和 TLR4 激动剂脂多糖进行处理。
URSA 患者 CD4CD25Foxp3 Tregs 比例降低，炎症反应增强。在易流产小鼠模型中，E5564 显著增加 CD4CD25Foxp3 Tregs 比例，降低炎症反应，增加 Foxp3 mRNA 和蛋白表达。脂多糖对易流产模型有不良影响。
这些数据表明，CD4CD25Foxp3 Tregs 通过 TLR4/核因子-κB 通路调节 URSA 中的免疫稳态，TLR4 拮抗剂 E5564 可能是治疗 URSA 的一种新型潜在药物。
